Search results for: cathepsin
#39362844 
2024/10/03
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Cathepsin B promotes Aβ proteotoxicity by modulating aging regulating mechanisms.
While the activities of certain proteases promote proteostasis and prevent neurodegeneration-associated phenotypes, the protease cathepsin B (CTSB) enhances proteotoxicity in Alzheimer's disease (AD) model mice, and its levels are elevated in brains of AD patients. How CTSB exacerbates the toxicity of the AD-causing Amyloid β (Aβ) peptide is controversial. Using an activity-based probe, aging-altering interventions and the nematode C. elegans, we discovered that the CTSB CPR-6 promotes Aβ proteotoxicity but mitigates the toxicity of polyQ stretches. While the knockdown of cpr-6 does not affect lifespan, it alleviates Aβ toxicity by reducing the expression of swsn-3 and elevating the level of the protein SMK-1, both involved in the regulation of aging. These observations unveil a mechanism by which CTSB aggravates Aβ-mediated toxicity, indicate that it plays opposing roles in the face of distinct proteotoxic insults and highlight the importance of tailoring specific remedies for distinct neurodegenerative disorders.Atif Ahmed Siddiqui, Emmanuelle Merquiol, Reut Bruck-Haimson, Joud Hirbawi, Hana Boocholez, Irit Cohen, Yonghong Yan, Meng Qiu Dong, Galia Blum, Ehud Cohen
2881 related Products with: Cathepsin B promotes Aβ proteotoxicity by modulating aging regulating mechanisms.
50 ug50 ug50 ug50 ug50 ug50 ug50 ug50 ug100 50 ug50 ug50 ug
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#39362330 2024/10/01
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Multi-omics and Bioinformatics for the Investigation of Therapeutic Mechanism of Roucongrong Pill against Postmenopausal Osteoporosis.
The Roucongrong Pill (RCRP), originating from the historical General Medical Collection of Royal Benevolence, is frequently used to treat postmenopausal osteoporosis (PMOP). Despite its prevalent application, the specific anti-osteoporotic mechanisms of RCRP remain to be elucidated.Tao Jiang, Chenhao Li, Yufen Li, Wanli Hu, Jiurui Guo, Xingchen Du, Qianting Meng, Xiaojuan Zhu, Wu Song, Junpeng Guo, Xin Su
1791 related Products with: Multi-omics and Bioinformatics for the Investigation of Therapeutic Mechanism of Roucongrong Pill against Postmenopausal Osteoporosis.
5 G5mg
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#39361421 2024/10/03
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Reactive microglia partially envelop viable neurons in prion diseases.
Microglia are recognized as the main cells in the central nervous system responsible for phagocytosis. The current study demonstrated that in prion disease, microglia effectively phagocytose prions or PrPSc during early preclinical stages. However, a critical shift occured in microglial activity during the late preclinical stage, transitioning from PrPSc uptake to establishing extensive neuron-microglia body-to-body cell contacts. This change was followed by a rapid accumulation of PrPSc in the brain. Microglia that enveloped neurons exhibited hypertrophic, cathepsin D-positive lysosomal compartments. However, most neurons undergoing envelopment were only partially encircled by microglia. Despite up to 40% of cortical neurons being partially enveloped at clinical stages, only a small percentage of envelopment proceeded to full engulfment. Partially enveloped neurons lacked apoptotic markers but showed signs of functional decline. Neuronal envelopment was independent of the CD11b pathway, previously associated with phagocytosis of newborn neurons during neurodevelopment. This phenomenon of partial envelopment was consistently observed across multiple prion-affected brain regions, various mouse-adapted strains, and different subtypes of sporadic Creutzfeldt-Jakob disease (sCJD) in humans. The current work describes a new phenomenon of partial envelopment of neurons by reactive microglia in the context of an actual neurodegenerative disease, not a disease model.Natallia Makarava, Tarek Safadi, Olga Bocharova, Olga Mychko, Narayan P Pandit, Kara Molesworth, Simone Baiardi, Li Zhang, Piero Parchi, Ilia V Baskakov
2216 related Products with: Reactive microglia partially envelop viable neurons in prion diseases.
500 tests500 tests500 tests96 tests500 tests500 tests500 tests96 tests500 tests500 tests
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#39360980 2024/10/03
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Osteogenic effect of alogliptin in chemical-induced bone loss: a tri-modal in silico, in vitro, and in vivo analysis.
To investigate the effects of Alogliptin in chemical-induced post-menopausal osteoporosis.Faraha Ahmed, Syed Sufian Ahmad, Mohammad Mumtaz Alam, Mohammad Shaquiquzzaman, Mohammad Altamish, Anuja Krishnan, Divya Vohora, Abul Kalam Najmi, Mohammad Ahmed Khan
1862 related Products with: Osteogenic effect of alogliptin in chemical-induced bone loss: a tri-modal in silico, in vitro, and in vivo analysis.
96 assays 100ul48 samples100 ul100ug50 ul100ug
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#39359476 2024/09/18
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Bidirectional two-sample Mendelian randomization analysis investigates causal associations between cathepsins and inflammatory bowel disease.
Cathepsins, key regulators of the pathology of gastrointestinal disorders such as inflammatory bowel disease (IBD), are a target protease that has attracted much attention in recent years. IBD is a chronic and relapsing inflammatory disorder of the gut. Traditional studies have shown a correlation between cathepsin and the risk of IBD, while the causal relationship remains unclear.Na Wang, Jun Liu, Bao Chai, Jianhong Yao, Xufang Du, Qi Mei, Xuena Wang
1056 related Products with: Bidirectional two-sample Mendelian randomization analysis investigates causal associations between cathepsins and inflammatory bowel disease.
96T1ml1ml16-22 Sample Kit24 samples4 Sample Kit1 module1 kit(96 Wells)
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#39357873 2024/10/02
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Physics-Based Protein Networks Might Recover Effectful Mutations─a Case Study on Cathepsin G.
Molecular dynamics simulations have been remarkably effective for observing and analyzing structures and dynamics of proteins, with longer trajectories being computed every day. Still, often, relevant time scales are not observed. Adequately analyzing the generated trajectories can highlight the interesting areas within a protein such as mutation sites or allosteric hotspots, which might foreshadow dynamics untouched by the simulations. We employ a physics-based protein network and propose that such a network can adequately analyze the protein dynamics. The analysis is conducted on simulations of cathepsin G and neutrophil elastase, which are remarkably similar but with different specificities. However, a single mutation in cathepsin G recovers the specificity of neutrophil elastase. The physics-based network built on the interactions between residues instead of the distances can pinpoint the active triad in the proteins studied. Overall, the network seems to capture the structural behavior better than purely distance-based networks.Fabian Schuhmann, Heloisa N Bordallo, Weria Pezeshkian
1953 related Products with: Physics-Based Protein Networks Might Recover Effectful Mutations─a Case Study on Cathepsin G.
1 Set100ul1 Set1 Set100.1mg100ug100.00 ug100ug
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#39350172 2024/09/30
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Loss of Lateral suppressor gene is associated with evolution of root nodule symbiosis in Leguminosae.
Root nodule symbiosis (RNS) is a fascinating evolutionary event. Given that limited genes conferring the evolution of RNS in Leguminosae have been functionally validated, the genetic basis of the evolution of RNS remains largely unknown. Identifying the genes involved in the evolution of RNS will help to reveal the mystery.Tengfei Liu, Zhi Liu, Jingwei Fan, Yaqin Yuan, Haiyue Liu, Wenfei Xian, Shuaiying Xiang, Xia Yang, Yucheng Liu, Shulin Liu, Min Zhang, Yuannian Jiao, Shifeng Cheng, Jeff J Doyle, Fang Xie, Jiayang Li, Zhixi Tian
1723 related Products with: Loss of Lateral suppressor gene is associated with evolution of root nodule symbiosis in Leguminosae.
100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized 5 G100ug Lyophilized1 mg50100 ul100ug Lyophilized100ug Lyophilized
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#39350121 2024/09/30
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Sulindac (K-80003) with nab-paclitaxel and gemcitabine overcomes drug-resistant pancreatic cancer.
The Nab-paclitaxel combined with gemcitabine (AG) regimen is the main chemotherapy regimen for pancreatic cancer, but drug resistance often occurs. Currently, the ability to promote sensitization in drug-resistant cases is an important clinical issue, and the strategy of repurposing conventional drugs is a promising strategy. This study aimed to identify a classic drug that targets chemotherapy resistance's core signaling pathways and combine it with the AG regimen to enhance chemosensitivity. We also aimed to find reliable predictive biomarkers of drug combination sensitivity. Using RNA sequencing, we found that abnormal PI3K/Akt pathway activation plays a central role in mediating resistance to the AG regimen. Subsequently, through internal and external verification of randomly selected AG-resistant patient-derived organoid (PDO) and PDO xenograft models, we discovered for the first time that the classic anti-inflammatory drug sulindac K-80003, an inhibitor of the PI3K/Akt pathway that we focused on, promoted sensitization in half (14/28) of AG-resistant pancreatic ductal adenocarcinoma cases. Through RNA-sequencing, multiplex immunofluorescent staining, and immunohistochemistry experiments, we identified cFAM124A as a novel biomarker through which sulindac K-80003 promotes AG sensitization. Its role as a sensitization marker is explained via the following mechanism: cFAM124A enhances both the mRNA expression of cathepsin L and the activity of the cathepsin L enzyme. This dual effect stimulates the cleavage of RXRα, leading to large amounts of truncated RXRα, which serves as a direct target of K-80003. Consequently, this process results in the pathological activation of the PI3K/Akt pathway. In summary, our study provides a new treatment strategy and novel biological target for patients with drug-resistant pancreatic cancer.Cheng-Ke Xie, Cheng-Yu Liao, Hong-Yi Lin, Yong-Ding Wu, Feng-Chun Lu, Xiao-Xiao Huang, Zu-Wei Wang, Ge Li, Cai-Feng Lin, Jian-Fei Hu, Yin-Hao Chen, Qiao-Wei Li, Li-Qun Chen, Hui-Xing Chen, Shi Chen
1062 related Products with: Sulindac (K-80003) with nab-paclitaxel and gemcitabine overcomes drug-resistant pancreatic cancer.
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#39346162 2024/06/20
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Assessment of the Effects of Host Modulatory Agents on Osteoclastogenesis.
Osteoclastogenesis, the formation of osteoclasts from precursor cells, plays a pivotal role in bone remodeling and associated pathologies like osteoporosis and rheumatoid arthritis. Host modulatory agents (HMAs) have emerged as potential therapeutic candidates for modulating osteoclastogenesis. However, their effects need comprehensive evaluation through studies.Tahsinul Haque
2711 related Products with: Assessment of the Effects of Host Modulatory Agents on Osteoclastogenesis.
5 G1 mg500 ug50 ug 50 ug 50 ug 50 ug 50ul (0.45mg/ml)0.1ml100 ul500 ug
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#39345818 2024/08/20
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STING-Activating Polymer-Drug Conjugates for Cancer Immunotherapy.
The stimulator of interferon genes (STING) pathway links innate and adaptive antitumor immunity and therefore plays an important role in cancer immune surveillance. This has prompted widespread development of STING agonists for cancer immunotherapy, but pharmacological barriers continue to limit the clinical impact of STING agonists and motivate the development of drug delivery systems to improve their efficacy and/or safety. We developed SAPCon, a STING-activating polymer-drug conjugate platform based on strain-promoted azide-alkyne cycloaddition of a novel dimeric amidobenzimidazole (diABZI) STING prodrug to hydrophilic poly(dimethylacrylamide--azido-ethylmethacrylate) polymer chains through a cathepsin B-responsive linker to increase circulation time and enable passive tumor accumulation. We found that intravenously administered SAPCon accumulated at tumor sites, where it was endocytosed by tumor-associated myeloid cells, resulting in increased STING activation in the tumor tissue. Consequently, SAPCon promoted an immunogenic tumor microenvironment characterized by increased frequency of activated macrophages and dendritic cells and improved infiltration of CD8 T cells, resulting in inhibition of tumor growth, prolonged survival, and enhanced response to anti-PD-1 immune checkpoint blockade in orthotopic breast cancer models. Collectively, these studies position SAPCon as a modular and programmable platform for improving the efficacy of systemically administered STING agonists for cancer immunotherapy.Taylor L Sheehy, Alexander J Kwiatkowski, Karan Arora, Blaise R Kimmel, Jacob A Schulman, Katherine N Gibson-Corley, John T Wilson